Fig. 1

mTOR signaling pathway regulated autophagy and EMT. PI3K activation is induced by interaction with a growth factor receptor, direct binding to Ras, also induced by NF-κB and TGF-β activation. Activation of the PI3K/AKT signaling pathway blocks autophagy by prohibiting mTOR. The PI3K/Akt pathway positively regulates WNT/β-catenin through phosphorylating the serine at residue 552 in β-catenin and the serine at residue 9 in glycogen synthase kinase 3β (GSK3β), which increases intracellular β-catenin levels that combine with E-cadherin to promote EMT. Moreover, The PI3K/Akt pathway activity up-regulates nuclear factors SNAIL and SLUG, contributing to EMT activation. GSK-3β directly induces autophagy by activating LKB1/AMPK and in turn prohibiting the PI3K/AKT/mTOR pathway. It also indirectly triggers autophagy through promoting the hydrolysis of β-catenin protein. LKB1/AMPK activation plays a critical role in stimulating autophagy via decreasing the ratio of p-mTOR/mTOR and p-p70s6k/p70s6k. In addition, LKB1/AMPK hinders EMT by inhibiting Smad2/3 and TGF-β activity. Ras protein mutation not only activates the Ras/Rac1/Mkk7/JNK pathway (with JNK in turn binding to Atg5/Atg7) but also induces the Ras/Raf1/MEK1/2/ERK signaling pathway, which results in autophagy activation and EMT enhancement